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Greater Suppression of Intraprostatic Androgens by Adding Abiraterone to LHRH Agonist in Patients With Prostate Cancer

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Key Points

  • Levels of intraprostatic androgens were significantly reduced by adding abiraterone to LHRH agonist treatment.
  • Residual T3- or lymph node–positive disease was observed in the majority of patients at prostatectomy pathologic staging.

In a phase II study reported in the Journal of Clinical Oncology, Taplin et al found that the addition of neoadjuvant abiraterone acetate (Zytiga) to the luteinizing hormone–releasing hormone (LHRH) agonist leuprolide acetate resulted in greater suppression of intraprostatic androgens in patients with intermediate- or high-risk localized prostate cancer.

In the study, 58 patients were randomly assigned to receive abiraterone plus leuprolide (n = 30) or leuprolide alone (n = 28) for 12 weeks followed by prostate biopsy. All patients then received 12 weeks of abiraterone plus leuprolide and underwent radical prostatectomy.

Intraprostatic Androgen Levels

At the 12-week biopsy, median prostatic levels of dihydrotestosterone (DHT; P < .001), testosterone (P = .02), dehydroepiandrosterone (P < .001), and Δ4-androstene-3,17-dione (P < .001) were significantly lower in the combination group. DHT and testosterone levels at prostatectomy after 24 weeks in both the 24-week and 12-week combined therapy groups were similar to those with abiraterone plus leuprolide at 12 weeks in the 24-week group.

Median prostate-specific antigen (PSA) levels at 12 weeks were lower in the combination group (0.10 vs 1.06 ng/mL), with levels being low at 24 weeks in both the 24-week and 12-week combination groups.

Residual Disease

Rates of pathologic complete response and minimal residual disease were 62% in patients receiving 24 weeks of combined therapy and 48% in those receiving 12 weeks. Many patients had significant volumes of residual tumor, with ypT3 disease found in 48% of patients receiving 24 weeks of combined treatment and in 59% receiving 12 weeks and lymph node involvement found in 24% and 11%.

The investigators concluded: “LHRH [agonist] plus [abiraterone acetate] treatment suppresses tissue androgens more effectively than LHRH [agonist] alone. Intensive intratumoral androgen suppression with LHRH [agonist] plus [abiraterone acetate] before prostatectomy for localized high-risk [prostate cancer] may reduce tumor burden.”

Mary-Ellen Taplin, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Ortho Biotech Oncology Research and Development, unit of Cougar Biotechnology (now Janssen Research and Development) and by others. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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